Pharmacologic/Toxicologic Effects

The effects of GB are attributed to several chemical constituents of the whole plant rather than to any
one individual component. These chemicals include many flavonoids (also called flavonol, flavone, or
flavonoid glycosides;ginkgo flavone glycosides; dimeric bioflavones), and the terpene lactones (also
called terpenoids; diterpenes; terpenes), including the ginkgolides and bilobalide (Ramassamy et al.,
1990; Houghton, 1994; Nemecz and Combest, 1997; Anonymous, 1998).
Nervous System Effects
The pharmacologic basis of the effects of GBE on brain function has been addressed in a number of
studies. One study (Ramassamy et al., 1990) showed

that dietary GBE 761 (prepared by the Henri Baeufour Institute) protected striatal dopaminergic
neurons of male Sprague-Dawley rats from damage caused by N-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP). MPTP, which has caused Parkinsonism in young drug abusers, is thought
to damage these neurons through formation of free radicals. The mechanism of GBE's protective effect
was attributed to an antioxidant action, rather than to prevention of neuronal uptake of MPTP. Whether
chronic GBE ingestion could prevent development of idiopathic Parkinson's disease in humans remains
to be seen.
This same extract has been investigated for the treatment of dementia. In one study (Le Bars et al.,
1997), 40-mg EGb 761 (Murdock, Springville, UT) tablets taken three times daily before meals was
compared to placebo in a double-blind, randomized trial in patients with mild to severe Alzheimer type
or multiinfarct dementia, diagnosed according to the Diagnostic and Statistical Manual of Mental
Disorders, 3rd edit., Revised (DSM-III-R) and International Statistical Classification of Diseases, 10th
Revision (ICD-10) criteria. The study lasted 52 wk, and patients were assessed at weeks 3, 26, and 52
using the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), the Geriatric
Evaluation by Relative's Rating Instrument (GERRI), and the Clinical Global Impression of Change
(CGIC), three validated rating instruments. Thus, participants' cognitive impairment, daily living and
social behavior, and general psychopathology were objectively evaluated. Modest improvement was
appreciated using ADAS-Cog and GERRI, but the CGIC score did not reveal improvement compared
to placebo. Adverse effects did not differ from those of placebo. The relatively large number of
dropouts (only 202 of 309 patients were assessed at week 52) raises questions about the validity of the
results. In addition, a meta-analysis of four double-blind, placebo-controlled studies including a total of
424 Alzheimer's patients found a small (3%) but clinically significant improvement on the ADAS -Cog
with 120240 mg of Ginkgo biloba administered for 36 mo (Oken et al., 1998). Given such small
benefits in light of ginkgo's association with spontaneous bleeding (See Section 3.5), more data are
needed before ginkgo can be recommended for the treatment of Alzheimer's disease.
The cognitive effects of ginkgo have also been assessed in nonAlzheimer's patients. In 18
nondemented elderly men with slight age-related memory loss based on immediate recall of three lists
of words, EGb 761 improved the speed of information processing based on ability to recall presented
word and pictures (Allain et al., 1993).
Anxiolytic effects have been demonstrated in animal models. The effect of Zingicomb(Mattern et
Partner, Starnberg, Germany), a combination product containing 24% ginkgo flavonoids and 23.5%
gingerols, administered

orally to rats at a dose of 0.5100 mg/kg was compared to the effects of placebo and diazepam
administered intraperitoneally at a dose of 1 mg/kg on anxiety-associated behaviors
(Hasenhrl et al., 1996). The rats were subjected to an elevated plus-maze consisting of
enclosed and open arms. The 0.5 mg/kg dose of Zingicombwas associated with rats spending
more time in the open arms and with more excursions toward the ends of the open arms as
compared to placebo. At a dose of 100 mg/kg, excursions to the ends of the open arms and
scanning (protruding the head over the edge of an open arm and looking around) were fewer.
These results were interpreted to mean that the preparation exhibited anxiolytic effects at a
dose of 0.5 mg/kg, but anxiogenic effects at 100 mg/ kg. Both the herbal product at a 0.5
mg/kg dose and diazepam increased the number of entries into the open arms, but unlike
diazepam, Zingicombdid not increase open arm scanning, nor did it attenuate risk assessment
(protruding the forepaws and head from an enclosed arm). These effects of the herbal
preparation were attributed to blockade of 5-hydroxytryptamine3(5-HT3; serotonin) receptors,
which has been shown in previous studies to produce similar results in the elevated plus-maze.
In addition, components of both ginger and ginkgo have been shown in several animal studies
to exert 5-HT3 receptor-blocking effects.
Vertigo and tinnitus have been successfully relieved with ginkgo at doses of 16160 mg/d for
3 mo (Kleijnen and Knipschild, 1992).